Huatuo Zaizao Pill Improves Neurological Function By Enhancing Angiogenesis In Stroke Rats

Huatuo Zaizao pill (HT), a traditional Chinese medicine, is widely used in China for the treatment of stroke patients. This study investigated the effect of HT on neurological function, ischemic area and angiogenesis in a rat model of cerebral ischemia-reperfusion (I/R) injury. Male rats were underwent a middle cerebral artery occlusion followed by reperfusion. Then the rats received intragastrically vehicle (for the sham group and model group) or HT (0.5, 1.0, or 2.0 g/kg), respectively. Neurological function was assessed by the Longa's method after 7-day treatment. Ischemic area was evaluated via triphenyl tetrazolium chloride staining. Double immunofluorescence staining for 4', 6-diamidino-2-phenylindole and von Willebrand factor (vWF) was performed. Protein expressions of hypoxia inducible factor 1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), vascular endothelial receptor tyrosine kinase Tie2, stromal cell derived factor-1 (SDF-1), and CXC chemokine receptor 4 (CXCR4) in the peri-infarct regions of cortex were analyzed by Western blotting. Compared with the model group, treatment with HT improved the neurological function and reduced the brain ischemic area in cerebral I/R-injured rats. The number of vWF positive vessels was significantly increased in the HT groups as compared with the model group. Levels of HIF-1 alpha, VEGF, Ang-1/p-Tie2 and SDF-1/CXCR4 were also enhanced after the 7-day HT treatment. These findings indicate that HT treatment could reduce the ischemic area and improve neurological function after stroke by enhancing angiogenesis.